Ribociclib Improves Overall Survival in HR+/HER2– Metastatic Breast Cancer Across Common Genomic and Clinical Subtypes

In updated biomarker and clinical subgroup analyses from the phase III MONALEESA trials, ribociclib demonstrated consistent improvements in overall survival when added to endocrine therapy in patients with HR-positive/HER2-negative advanced breast cancer.

Treatment with the CDK4/6 inhibitor ribociclib plus ET significantly improved overall survival (OS) relative to ET alone in the landmark phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials, which represented the spectrum of premenopausal and postmenopausal patients with HR-positive, HER2-negative advanced breast cancer. [1][2][3] Understanding how the magnitude of benefit with CDK4/6 inhibitor therapy varies by clinical and genomic subtype may enable oncologists to develop personalized treatment plans. In subgroup analyses from the MONALEESA trials, researchers evaluated OS outcomes by intrinsic tumor subtype and metastatic site. 4,5

Ribociclib and Overall Survival by Intrinsic Tumor Subtype
Lisa A. Carey, M.D., of the University of North Carolina at Chapel Hill, presented results from an analysis of overall survival in the MONALEESA-2, -3, and -7 trials by intrinsic tumor subtype. 4 In the retrospective exploratory analysis, tumor samples from patients in the MONALEESA trials (n = 997) underwent gene expression profiling with the Prediction Analysis of Microarray 50 (PAM50) assay. Luminal A was the most common subtype (54.4%), followed by luminal B (27.9%), HER2-enriched (14.7%), and basal-like (3.0%).
Intrinsic tumor subtype was prognostic for survival outcomes (p < .001) after adjusting for clinical covariates. Patients with the basal-like subtype did not appear to benefit from CDK 4/6 inhibitor therapy, whereas those with HER2enriched tumors experienced the greatest magnitude of survival benefit.
The phase III HARMONIA trial will evaluate the activity of ribociclib plus ET in patients with HER2-enriched tumors, with the goal of providing further insight on developing personalized treatment plans for patients with HR+/HER2metastatic breast cancer.

Ribociclib and Overall Survival by Metastatic Site
The phase III MONALEESA-2 trial evaluated first-line ribociclib plus letrozole, compared with placebo plus letrozole, in 668 postmenopausal women with HR+/HERadvanced breast cancer. In the overall study population, ribociclib significantly improved OS by 24% compared with ET alone (HR, 0.76; p = .004). 1 Joyce O'Shaughnessy, M.D., of Texas Oncology-Baylor University Medical Center, presented findings from an exploratory analysis of OS by metastatic site in the MONALEESA-2 trial. 5 Results showed a consistent survival benefit in favor of ribociclib plus letrozole relative to letrozole alone, regardless of metastatic site ( Table 2). All comparisons favored
Results also favored treatment with ribociclib regardless of the number of metastatic sites. Compared with letrozole alone, ribociclib plus letrozole improved OS for patients with <3 metastatic sites (HR, 0.78; 95% CI, 0.61-1.00) and for patients with ≥3 metastatic sites (HR, 0.71; 95% CI, 0.51-0.98). The survival benefit with ribociclib was similarly consistent regardless of prior adjuvant or neoadjuvant chemotherapy or endocrine therapy.
Overall findings from the MONALEESA biomarker and clinical subgroup analyses demonstrate consistent and long-term improvements in OS with the addition of ribociclib to ET in patients with HR+/HR-advanced breast cancer. 4,5